Continued support is sought for a multifaceted study of human and experimentally induced muscle diseases with light, phase and electron microscopy, light and electron microscopic cytochemistry, immuno-electron microscopy, tissue culture methods and correlative biochemical and electrophysiologic investigations. The ultrastructure reactions of the muscle fiber organelles and of the neuromuscular junction will be investigated and quantitated by morphometric methods. Well recognized as well as new and hitherto undescribed diseases will be intensively studied. Myasthenia gravis and its experimental autoimmune model will be investigated with methods involving the ultrastructural localization of the acetylcholine receptor (AChR) protein and antibodies bound to the postsynaptic region. The interaction between AChR and antibody, the pathogenesis of the destructive changes at the end-plate and the mechanisms of impaired neuromuscular transmission and of recovery will be analyzed. In Duchenne dystrophy cultured muscle fibers will be examined for evidences of the plasma membrane abnormalities observed in vivo. In the syndrome of carnitine deficiency the morphologic expression of the disease and the mechanism of carnitine transport will be investigated in cultured fibers. In a newly discovered myasthenic syndrome associated with end-plate acetyl cholinesterase (AChE) deficiency the molecular forms of AChE in muscle and erythrocytes will be studied; and the expression of the defect in aneural muscle cultures and in cultured fibers innervated by rodent nerve will be examined.